Instaictlons); Although research has demonstrated protocol changes to improve stone comminution and reduce tissue injury in shock wave lithotripsy (SWL), such changes have been slowly adopted. An important reason Is that the users do not have real-time feedback on the effect of a protocol change. Accordingly, we propose the development of a variety of feedback techniques to improve patient outcomes. In Specific Aim (SA) 1, we propose to develop a novel imaging technique that promises to permit real-time localization of stones as small as 2 mm, if not smaller. We have discovered (or rediscovered) an artifact, called twinkling that occurs when Doppler ultrasound is used to image a stone in which a multi-colored image is generated that accurately replicates the size of the stone. In SA2, we propose to develop an instrument to send, through the lithotripter focus, ultrasound pulses that would be reflected and subsequently detected only when a stone was located at the focus; using these pulses as a trigger, shock waves would only be applied to stones, and would thus account for stone movement, including the effects of respiration. In SA3, we propose to develop a passive acoustic receiver that interrogates the sound scattered from the stone by the applied shock waves and correlates the frequency content of this sound with the size of the fragments. This concept would permit the user to learn when the stone was sufficiently comminuted and treatment could be terminated. In SA4, we address residual stone fragments and the challenge to current lithotripters in treating stones in the lower calyx, specifically by utilizing radiation forces to move stones and fragments within the collecting system of the kidney itself. Finally, in SAS, we propose to investigate a new mechanism for shock-wave-induced tissue injury; viz., stresses induced by tension, rather than compression. Our preliminary studies have demonstrated that cavitation damage to blood vessels probably results from invagination ofthe vessel wall when the bubble collapses, rather than stresses imposed by bubble expansion or reentrant liquid jets. Overall, the proposal takes novel concepts, quantifies basic science techniques, and generates practical solutions to areas where significant improvement can be made in clinical lithotripsy and patient outcomes. RELEVANCE (See Instructions): Shock wave lithotripsy (SWL) is the most common treatment for a prevalent disease, kidney stones. Yet like other treatments, SWL has side-effects. The proposal goal is to provide urologists new feedback so side- effects can be minimized and a broader spectrum of patients can be treated. The effect on public health will be an increase in successful outcomes and a decrease in retreatments, complications, and costly alternative treatments .